The long-term goals of this proposal are to investigate the mechanisms by which: a) Fc fragments of immunoglobulin (Ig) activate human bone marrow-derived (B) lymphocytes, thymus-derived (T) lymphocytes, and monocytes; b) Fc fragments regulate in vitro immune responses; c) map the various biological functions associated with Fc fragments to discrete regions of the molecule. Upon determining the active sequence, peptides will be synthesized and assessed for biological activity. The observation that Fc fragments modulate in vitro humoral and cell-mediated immune responses suggests that this physiologic molecule may be useful as an immunotherapeutic agent in immunodeficency states and cancer management. In order to determine the in vivo applicability of fc fragments as an immune response modifier, it is necessary to understand how Fc fragments and Fc fragment-induced biologically active mediators interact with lymphoid cells and each other in regulating immune reactivity. A comprehensive program has been outlined to use Fc fragments as model system for human B cell activation.